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European Journal of Obstetrics,... Aug 2023Leiomyomas (fibroids), the most common benign solid tumours in females, originate from the myometrium and are associated with poor quality of life for patients. The... (Review)
Review
BACKGROUND
Leiomyomas (fibroids), the most common benign solid tumours in females, originate from the myometrium and are associated with poor quality of life for patients. The current management of uterine leiomyomas mainly includes surgical interventions such as hysterectomy and myomectomy, either by laparoscopy or laparotomy, which have several complications and are not ideal for preserving fertility. Therefore, there is a need to develop or repurpose medical treatments that do not require surgical intervention.
OBJECTIVE
Many drugs are used to treat the symptoms associated with uterine fibroids. The main objective of this systematic review is to give an up-to-date account of potential pharmacological agents (non-surgical methods) for the management of uterine leiomyomas.
SEARCH STRATEGY
PubMed was searched for scientific and clinical literature using the keyword 'uterine fibroids' along with the drug names described in each section. For example, 'uterine fibroids' and 'ulipristal acetate' were the keywords used to search for literature on ulipristal acetate (UPA).
RESULTS
Various preclinical and clinical studies have shown that some drugs and herbal formulations exhibit activity in the management of uterine leiomyomas. Recent studies found that drugs such as UPA, elagolix, EC313, asoprisnol, nutritional supplements and herbal preparations were helpful in treating the symptoms associated with uterine leiomyomas.
CONCLUSION
Many drugs show efficacy in patients with symptomatic uterine fibroids. UPA is one of the most studied and prescribed medicines for uterine fibroids; however, its usage has been restricted due to a few recent incidences of hepatic toxicity. Herbal drugs and natural supplements have also shown promising effects on uterine fibroids. The synergistic effects of nutritional and herbal supplements have been reported in certain cases, and should be studied in detail. Further research is warranted to identify the mode of action of the drugs, and to determine the precise conditions that would explain the causes of toxicity in some patients.
Topics: Female; Humans; Uterine Neoplasms; Quality of Life; Leiomyoma; Uterine Myomectomy; Acetates
PubMed: 37385088
DOI: 10.1016/j.ejogrb.2023.06.021 -
Journal of Clinical Medicine Sep 2023Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments... (Review)
Review
Uterine Adenomyosis is a benign condition characterized by the presence of endometrium-like epithelial and stromal tissue in the myometrium. Several medical treatments have been proposed, but still, no guidelines directing the management of adenomyosis are available. While a hysterectomy is typically regarded as the definitive treatment for adenomyosis, the scarcity of high-quality data leaves patients desiring fertility with limited conservative options. Based on the available data, the levonorgestrel-IUD appears to offer the most favorable outcomes. Other treatments, including GnRH antagonists, dienogest, prolactin, and oxytocin modulators, show promise; however, further data are required to establish their efficacy definitively. Furthermore, there are many emerging therapies that have been developed that seem worthy of consideration in the near future. The aim of this narrative review was to explore the current medical treatments available for adenomyosis and to provide a glimpse of future therapies under assessment. For this scope, we performed a literature search on PubMed and Medline from incept to September 2022 using the keywords: "medical treatment", "non-steroidal anti-inflammatory", "progesterone intrauterine device", "dienogest", "combined oral contraceptives", "gonadotropin releasing hormone agonist", "gonadotropin releasing hormone antagonist", "danazol", "aromatase inhibitors", "ulipristal acetate", "anti-platelet therapy", "dopamine", "oxytocin antagonists", "STAT3", "KRAS", "MAPK", "micro-RNA", "mifepristone", "valproic acid", "levo-tetrahydropalamatine", and "andrographolide". The search was limited to articles in English, with subsequent screening of abstracts. Abstracts were screened to select relevant studies.
PubMed: 37834773
DOI: 10.3390/jcm12196130 -
Fetal and Pediatric Pathology Dec 2023To investigate the relaxation responses mediated by L-type Ca2+ channels and big-conductance Ca-activated K (BKCa) channels and histological changes in the human...
To investigate the relaxation responses mediated by L-type Ca2+ channels and big-conductance Ca-activated K (BKCa) channels and histological changes in the human umbilical artery (HUA) and myometrium smooth muscle isolated from pregnancies complicated with intrauterine growth restriction (IUGR). The muscle reactivity and the histology of the smooth muscle of the HUA and myometrium retrieved from 14 women with IUGR and 14 controls were investigated by the isolated tissue bath and immunohistochemical method. In HUA, the maximum relaxation responses and pD2 values of nifedipine and NS11021 (BKCa channel opener) were significantly increased and significant histopathological changes are observed in the IUGR group.: The pathogenesis of IUGR might be associated with the impairment in the functional responses of L-type Ca2+ channels and BKCa channels in HUA smooth muscle. The increased staining of myometrium and UC with HIF-1α in IUGR may indicate apoptosis, histological damage, and impaired fetal growth.
Topics: Pregnancy; Humans; Female; Myometrium; Umbilical Arteries; Fetal Growth Retardation; Calcium; Muscle, Smooth
PubMed: 37578058
DOI: 10.1080/15513815.2023.2245892 -
International Journal of Molecular... Dec 2023Uterine aging is the process of the senescence of uterine tissue, observed in all middle-aged mammals. Since the aging-related changes in the uterus are associated with... (Review)
Review
Uterine aging is the process of the senescence of uterine tissue, observed in all middle-aged mammals. Since the aging-related changes in the uterus are associated with infertility and poor pregnancy outcomes, with a lack of studies discussing uterine aging, authors reviewed uterine aging and its consequences on reproduction. MEDLINE, Scopus, and PubMed searches during the years 1990-2023 were performed using a combination of keywords and terms on such topics. According to the author's evaluation, articles were identified, selected, and included in this narrative review. The aging process has an unfavorable impact on the uterus of mammals. There are different and selected molecular pathways related to uterine aging in humans and animals. Uterine aging impairs the function of the uterine myometrium, neurofibers of the human uterus, and human endometrium. These biological pathways modulate oxidative stress, anti-inflammatory response, inflammation, mitochondrial function, DNA damage repair, etc. All these dysregulations have a role in poorer reproductive performance and pregnancy outcomes in older mammals. The most recent data suggest that uterine aging is accompanied by genetic, epigenetic, metabolic, and immunological changes. Uterine aging has a negative impact on the reproductive performance in mammalian species, but it could be potentially modulated by pharmacological agents, such as quercetin and dasatinib.
Topics: Animals; Female; Humans; Middle Aged; Pregnancy; Aged; Uterus; Aging; Endometrium; Mammals; Biological Products
PubMed: 38203493
DOI: 10.3390/ijms25010322 -
International Journal of Gynecological... Oct 2023Placenta accreta spectrum encompasses cases where the placenta is morbidly adherent to the myometrium. Placenta percreta, the most severe form of placenta accreta... (Review)
Review
Placenta accreta spectrum encompasses cases where the placenta is morbidly adherent to the myometrium. Placenta percreta, the most severe form of placenta accreta spectrum (grade 3E), occurs when the placenta invades through the myometrium and possibly into surrounding structures next to the uterine corpus. Maternal morbidity of placenta percreta is high, including severe maternal morbidity in 82.1% and mortality in 1.4% in the recent nationwide U.S. statistics. Although cesarean hysterectomy is commonly performed for patients with placenta accreta spectrum, conservative management is becoming more popular because of reduced morbidity in select cases. Treatment of grade 3E disease involving the urinary bladder, uterine cervix, or parametria is surgically complicated due to the location of the invasive placenta deep in the maternal pelvis. Cesarean hysterectomy in this setting has the potential for catastrophic hemorrhage and significant damage to surrounding organs. We propose a step-by-step schema to evaluate cases of grade 3E disease and determine whether immediate hysterectomy or conservative management, including planned delayed hysterectomy, is the most appropriate treatment option. The approach includes evaluation in the antenatal period with ultrasound and magnetic resonance imaging to determine suspicion for placenta previa percreta with surrounding organ involvement, planned cesarean delivery with a multidisciplinary team including experienced pelvic surgeons such as a gynecologic oncologist, intra-operative assessment including gross surgical field exposure and examination, cystoscopy, and consideration of careful intra-operative transvaginal ultrasound to determine the extent of placental invasion into surrounding organs. This evaluation helps decide the safety of primary cesarean hysterectomy. If safely resectable, additional considerations include intra-operative use of uterine artery embolization combined with tranexamic acid injection in cases at high risk for pelvic hemorrhage and ureteral stent placement. Availability of resuscitative endovascular balloon occlusion of the aorta is ideal. If safe resection is concerned, conservative management including planned delayed hysterectomy at around 4 weeks from cesarean delivery in stable patients is recommended.
Topics: Female; Pregnancy; Humans; Placenta Accreta; Placenta; Placenta Previa; Myometrium; Cesarean Section; Hysterectomy; Retrospective Studies
PubMed: 37524496
DOI: 10.1136/ijgc-2023-004615 -
Fertility and Sterility Jan 2024
Topics: Humans; Female; Myometrium
PubMed: 37979609
DOI: 10.1016/j.fertnstert.2023.11.016 -
Ultrasound in Obstetrics & Gynecology :... Nov 2023Two-dimensional (2D) transvaginal ultrasound (TVS) is an accessible and cost-effective diagnostic tool for the detection of adenomyosis. Different ultrasound features...
OBJECTIVE
Two-dimensional (2D) transvaginal ultrasound (TVS) is an accessible and cost-effective diagnostic tool for the detection of adenomyosis. Different ultrasound features related to adenomyosis have been described, but the predictive value of each ultrasound sign and their combinations requires further investigation. We aimed to analyze the accuracy of 2D-TVS and describe possible combinations of ultrasound signs with a high predictive value in the diagnosis of adenomyosis.
METHODS
This was a prospective multicenter study of patients scheduled for laparoscopic hysterectomy who had been examined using standardized 2D-TVS at nine expert centers specializing in the diagnosis and treatment of endometriosis. 2D-TVS examination included nine typical adenomyosis ultrasound features, comprising heterogeneous myometrium, myometrial linear striations, myometrial cysts, subendometrial microcysts, asymmetrical myometrial thickening, uterine enlargement, the 'question mark sign', thickening of the junctional zone and hyperechoic myometrial spots, in order to predict or exclude the presence of adenomyosis. Ultrasound examination results were compared with histology after hysterectomy. The diagnostic reliability of the nine ultrasound signs and their combinations, and the influence of concurrent fibroids on the accuracy of the results, were analyzed.
RESULTS
A total of 202 patients were enrolled into the study. Histopathological examination revealed adenomyosis in 130 patients (64.4%). The accuracy of prediction of adenomyosis by 2D-TVS examination using all signs was 63.4% (positive predictive value, 71.5%; negative predictive value, 48.6%; sensitivity, 71.5%; specificity, 48.6%). Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy (55.7-62.1%) as individual ultrasound signs for the prediction of adenomyosis. The combination of the most accurate ultrasound signs (subendometrial microcysts, myometrial cysts and heterogeneous myometrium) improved the specificity of prediction (86.1%) when compared with that of these three single markers (35.2-81.7%). Uterine enlargement and asymmetry showed both low sensitivity (60.8% and 52.3%, respectively) and specificity (41.7% and 49.3%, respectively) as individual sonographic signs.
CONCLUSIONS
Heterogeneous myometrium, myometrial cysts, subendometrial microcysts and hyperechoic myometrial spots showed the highest accuracy for the detection of adenomyosis in this study, while uterine enlargement and asymmetry led to high false-positive and false-negative results. A combination of ultrasound features including the most accurate signs increases specificity. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Female; Humans; Adenomyosis; Cysts; Endometriosis; Myometrium; Prospective Studies; Reproducibility of Results; Sensitivity and Specificity; Ultrasonography
PubMed: 36920431
DOI: 10.1002/uog.26197 -
Facts, Views & Vision in ObGyn Dec 2023Adenomyosis is a disease defined by histopathology, mostly of hysterectomy specimens, and classification is challenged by the disagreement of the histologic definition....
Adenomyosis is a disease defined by histopathology, mostly of hysterectomy specimens, and classification is challenged by the disagreement of the histologic definition. With the introduction of Magnetic Resonance Imaging (MRI) and two- and three-dimensional ultrasound, the diagnosis of adenomyosis became a clinical entity. In MRI and US, adenomyosis ranges from thickening of the inner myometrium or junctional zone to nodular, cystic, or diffuse lesions involving the entire uterine wall, up to a well-circumscribed adenomyoma or a polypoid adenomyoma. The absence of an accepted classification and the vague and inconsistent terminology hamper basic and clinical research. The sub-endometrial halo seen at US and MRI is a distinct entity, differing from the outer myometrium by its increased nuclear density and vascular structure. The endometrium and the sub-endometrial muscularis or archimetra are of Müllarian origin, while the outer myometrium is non-Mullerian mesenchymal. The junctional zone (JZ) is important for uterine contractions, conception, implantation, and placentation. Thickening of the JZ can be considered inner myometrium adenomyosis, with or without endometrial invasion. Changes in the JZ should be considered a different entity than myometrial clinically associated with impaired conception, implantation, abnormal uterine bleeding, pelvic pain and obstetrical outcome. Pathology of the basal endometrium and JZ is a separate entity and should be identified as an endo-myometrial unit disorder (EMUD).
PubMed: 38128089
DOI: 10.52054/FVVO.15.4.109 -
BMC Women's Health Sep 2023Intravenous leiomyomatosis (IVL) is a rare and specific type of smooth muscle tumor that is histologically benign but has a malignant biological behavior. It is commonly...
BACKGROUND
Intravenous leiomyomatosis (IVL) is a rare and specific type of smooth muscle tumor that is histologically benign but has a malignant biological behavior. It is commonly associated with a history of uterine leiomyomas.
CASE PRESENTATION
A 36-year-old woman, G1P1, presented to the hospital with left lower abdominal pain for 2 months and she has accepted hysteroscopic myomectomy about 1 year ago. Ultrasound venography, echocardiography and computed tomography venography (CTV) of inferior vena cava were performed, which revealed IVL located in left intramural myometrium walls growing along the left ovarian vein reaching the level of the lumbar 5-sacral 1 disc. Laparoscopic bilateral salpingo-oophorectomy and hysterectomyis were scheduled. The IVL in the left ovarian vein and parauterine venous plexus were detected and excised completely during surgery. IVL was diagnosed by postoperative pathology and immunohistochemistry. The patient recovered well after surgery. No surgical-related or anesthesia-related complications occurred.The 3-month follow-up CTV of inferior vena cava and echocardiography examination revealed normal.
CONCLUSIONS
The cause of IVL is unknown, this observation demonstrates that hysteroscopic myomectomy might lead to the occurrence of IVL.
Topics: Female; Humans; Adult; Leiomyomatosis; Abdominal Pain; Echocardiography; Myometrium; Pelvis
PubMed: 37697329
DOI: 10.1186/s12905-023-02618-3 -
Best Practice & Research. Clinical... Aug 2023The increase in caesarean sections (CS) has resulted in an increase in women with a uterine niche. The exact aetiology of niche development has yet to be elucidated but... (Review)
Review
The increase in caesarean sections (CS) has resulted in an increase in women with a uterine niche. The exact aetiology of niche development has yet to be elucidated but is likely multifactorial. This study aimed to give a systematic overview of the available literature on histopathological features, risk factors and results of preventive strategies on niche development to gain more insight into the underlying mechanisms. Based on current published data histopathological findings associated with niche development were necrosis, fibrosis, inflammation, adenomyosis and insufficient approximation. Patient-related risk factors included multiple CS, BMI and smoking. Labour-related factors were CS before onset of labour, extended cervical dilatation, premature rupture of membranes and presenting part of the fetus at CS below the pelvic inlet. Preventive strategies should focus on the optimal level of incision, training of surgeons and full-thickness closure of the myometrium (single or double-layer) using non-locking sutures. Conflicting data exist concerning the effect of endometrial inclusion. Future studies without heterogeneity in population, using standardized performance of the CS after proper training and using standardized niche evaluation with a relevant core outcome set are required to allow meta-analyses and to develop evidence-based preventive strategies. These studies are needed to reduce the prevalence of niches and prevent complications in subsequent pregnancies such as caesarean scar pregnancies.
Topics: Pregnancy; Female; Humans; Cicatrix; Uterus; Cesarean Section; Myometrium; Risk Factors
PubMed: 37385157
DOI: 10.1016/j.bpobgyn.2023.102363